Medicines

Background: Sexually transmitted gonorrhea, caused by the Gram-negative diplococcus Neisseria gonorrhoeae, continues to be a serious global health challenge despite efforts to eradicate it. Multidrug resistance among clinical N. gonorrhoeae isolates has limited treatment options, and attempts to develop vaccines have not been successful. Methods: A search of published literature was conducted, and information extracted to provide an update on the status of therapeutics and vaccine development for gonorrheal infection. Results: Recommended pharmacological treatment for gonorrhea has changed multiple times due to increasing acquisition of resistance to existing antibiotics by N. gonorrhoeae. Only broad-spectrum cephalosporin-based combination therapies are currently recommended for treatment of uncomplicated urogenital and anorectal gonococcal infections. With the reported emergence of ceftriaxone resistance, successful strategies addressing the global burden of gonorrhea must include vaccination. Century-old efforts at developing an effective vaccine against gonorrhea, leading to only four clinical trials, have not yielded any successful vaccine. Conclusions: While it is important to continue to explore new drugs for the treatment of gonorrhea, the historical trend of resistance acquisition suggests that any long-term strategy should include vaccine development. Advanced technologies in proteomics and in silico approaches to vaccine target identification may provide templates for future success. Full article

Background: Stargardt Disease is the most common inherited macular degeneration, typically resulting in progressive central vision loss and legal blindness at an early age. We report regarding 34 eyes with Stargardt Disease treated in the Stem Cell Ophthalmology Treatment Study (SCOTS and SCOTS2). Methods: Autologous bone marrow was processed, separating the stem cell fraction which was provided Arms using retrobulbar, subtenons, intravitreal or subretinal and intravenous. The follow-up period was one year. Results: Of the 34 treated eyes, 21 (61.8%) improved, 8 (23.5%) remained stable, and 5 (14.7%) showed continued progression of their disease. Results were statistically significant with p = 0.0004. The average central vision improvement following treatment was 17.96% (95%CI, 16.39–19.53%) and ranged up to 80.5%. Of 17 patients treated, 13 (76.5%) showed visual acuity improvement in one or both eyes, 3 patients (17.6%) showed no net loss, and 1 worsened as a consequence of disease progression; 94.1% of patients had improved vision or remained stable. There were no adverse events. Conclusions: Patients with Stargardt Disease may potentially benefit from autologous bone marrow-derived stem cells (BMSC) as provided in SCOTS. Improvement or stabilization of vision was found to occur for the vast majority of reported patients and findings were highly statistically significant. Full article

Background: Genetic hypomyelinating diseases are a heterogeneous group of disorders involving the white matter. One infantile hypomyelinating leukoencephalopathy is associated with the homozygous variant (Cys4-to-Ser (C4S)) of the c11orf73 gene. Methods: We observed that in mouse oligodendroglial FBD-102b cells, the C4S mutant proteins but not the wild type ones of C11orf73 are microscopically localized in the lysosome. And, they downregulate lysosome-related signaling in an immunoblotting technique. Results: The C4S mutant proteins specifically interact with Filamin A, which is known to anchor transmembrane proteins to the actin cytoskeleton; the C4S mutant proteins and Filamin A are also observed in the lysosome fraction. While parental FBD-102b cells and cells harboring the wild type constructs exhibit morphological differentiation, cells harboring C4S mutant constructs do not. It may be that morphological differentiation is inhibited because expression of these C4S mutant proteins leads to defects in the actin cytoskeletal network involving Filamin A. Conclusions: The findings that leukoencephalopathy-associated C11ORF73 mutant proteins specifically interact with Filamin A, are localized in the lysosome, and inhibit morphological differentiation shed light on the molecular and cellular pathological mechanisms that underlie infantile hypomyelinating leukoencephalopathy. Full article

Background: One of the lesser recognized complications of diabetes mellitus are musculoskeletal (MSK) complications of the upper and lower extremity. No prevalence studies have been conducted in general practice. Thus, the aim of this study was to investigate the prevalence of upper extremity MSK disorders in patients with type 2 diabetes (T2DM) in the Netherlands. Methods: We conducted a cross-sectional study with two different approaches, namely a representative Dutch primary care medical database study and a questionnaire study among patients with T2DM. Results: In the database study, 2669 patients with T2DM and 2669 non-diabetes patients were included. MSK disorders were observed in 16.3% of patients with T2DM compared to 11.2% of non-diabetes patients (p < 0.001, OR 1.53, 95% CI 1.31, 1.80). In the questionnaire study, 200 patients with T2DM were included who reported a lifetime prevalence of painful upper extremity body sites for at least four weeks of 67.3%. Conclusion: We found that upper extremity MSK disorders have a high prevalence in Dutch patients with T2DM presenting in general practice. The prevalence ranges from 16% based on GP registered disorders and complaints to 67% based on self-reported diagnosis and pain. Early detection and treatment of these disorders may play a role in preventing the development of chronic MSK disorders. Full article

Background: Primary small cell carcinoma of the kidney (PSCCK) is exceedingly rare and data on disease characteristics and outcomes are sparse. This study examines a nationally-representative cancer registry to better characterize PSCCK. Methods: We queried the National Cancer Database to identify patients with histology-confirmed PSCCK from 2004 to 2015. Adjusted Cox proportional hazards regression and Kaplan–Meier analyses were employed to assess predictors of mortality and estimate median survival time, respectively. Results: A total of 110 patients were included (47:53% female:male, 77% ≥60 years of age, 86% Caucasian). Significant predictors of mortality included female sex, age 60–69 years, treatment at an Integrated Network Cancer Program, stage cM1, and lack of surgical and chemoradiotherapy treatment. Independent protective factors were high socioeconomic status and treatment at an Academic Research Program. The estimated median overall survival time was 9.31 (95% CI 7.28–10.98) months for all patients. No differences in estimated survival time were observed across individual treatment modalities among those patients who underwent treatment (p = 0.214). Conclusions: PSCCK is an aggressive malignancy with a median survival time of less than one year. Future studies that correlate clinical tumor staging with specific treatment modalities are needed to optimize and individualize management. Full article

Renal cell carcinoma is a malignant tumor that arises in the kidney parenchyma. For many years, sunitinib has represented the mainstay of medical treatment for metastatic renal cell carcinoma. Herein, we present the case of a 66-year-old woman with metastatic clear cell renal carcinoma undergoing treatment with sunitinib for two years that developed encephalic leukocytoclastic vasculitis, probably due to a paraneoplastic syndrome. Full article

Background: Acute kidney injury (AKI) is a serious complication of COVID-19. Methods: Records of hospitalized adult patients with confirmed SARS-CoV-2 infection from 1 March to 31 May 2020 were retrospectively reviewed. Results: Of 283 patients, AKI occurred in 40.6%. From multivariate analyses, the risk factors of AKI in COVID-19 can be divided into: (1) demographics/co-morbidities (male, increasing age, diabetes, chronic kidney disease); (2) other organ involvements (transaminitis, elevated troponin I, ST segment/T wave change on electrocardiography); (3) elevated biomarkers (ferritin, lactate dehydrogenase); (4) possible bacterial co-infection (leukocytosis, elevated procalcitonin); (5) need for advanced oxygen delivery (non-invasive positive pressure ventilation, mechanical ventilation); and (6) other critical features (ICU admission, need for vasopressors, acute respiratory distress syndrome). Most AKIs were due to pre-renal (70.4%) and intrinsic (34.8%) causes. Renal replacement therapy was more common in intrinsic AKI. Both pre-renal (HR 3.2; 95% CI 1.7–5.9) and intrinsic AKI (HR 7.7; 95% CI 3.6–16.3) were associated with higher mortality. Male, stage 3 AKI, higher baseline and peak serum creatinine and blood urea nitrogen were prevalent in intrinsic AKI. Urine analysis and the fractional excretion of sodium and urea were not helpful in distinguishing intrinsic AKI from other causes. Conclusions: AKI is very common in COVID-19 and is associated with higher mortality. Characterization of AKI is warranted due to its diverse nature and clinical outcome. Full article

Erectile Dysfunction (ED) is the persistent inability to attain and maintain an erection sufficient to permit satisfactory sexual performance, causing tremendous effects on both patients and their partners. The pathophysiology of ED remains a labyrinth. The underlying mechanisms of ED may be vasculogenic, neurogenic, anatomical, hormonal, drug-induced and/or psychogenic. Neurogenic ED consists of a large cohort of ED, accounting for about 10% to 19% of all cases. Its diversity does not allow an in-depth clarification of all the underlying mechanisms nor a “one size fits all” therapeutical approach. In this review, we focus on neurogenic causes of ED, trying to elucidate the mechanisms that lie beneath it and how we manage these patients. Full article

Erectile dysfunction (ED) is a disorder that affects the quality of life and the sexual relations of more than half of the male population aged over 40 years. The prediction regarding the incidence of ED is devastating as it is expected that this disorder will affect more than 300 million men in the next five years. Several studies have suggested the use of stem cells for the treatment of ED and showed that this type of treatment is promising in terms of damaged tissue repair as well as of clinical efficacy; however, there are several gaps in the knowledge and evidence is lacking. In order to highlight a few of them in this review, we performed a research of the literature focusing on currently available clinical studies regarding the clinical efficacy of stem cell administration for the treatment of ED. We reviewed the methods of administration, the cell types used in the performed clinical trials and the safety and efficiency of such procedures. We conclude that there are rapidly expanding and promising results from the reported clinical studies indicating that stem cells could indeed be a potential treatment for patients with ED although more studies are necessary. Full article

Helicobacter pylori (H. pylori) is a bacterial pathogen implicated in gastritis, gastric ulceration, and gastric carcinoma. This study aimed to synthesize literature in providing evidence on the causative role of H. pylori in gastric carcinoma development. This study is based on assessing public literature using an applied meta-analysis, namely, quantitative evidence synthesis (QES). The analytic procedure uses DerSimonian-Laird, including assessing heterogeneity. The QES also utilizes meta-regression and the environmental effect associated with H. pylori in gastric cancer development. Eighteen studies are included in the QES. There is increased prevalence of H. pylori exposure among the cases. The heterogeneity between the CES and individual effect sizes is also significant. Despite controlling for the confoundings, there is increased exposure to H. pylori among the gastric cancer cases, regardless of the differences in the geographic location. H. pylori in this synthesized literature illustrates the contributory role of this microbe in gastric carcinoma. Additionally, regardless of geographic locale, namely, South Korea or Spain, H. pylori is implicated in gastric cancer development. Full article

Background: Fentanyl can induce acute opioid tolerance and postoperative hyperalgesia when administered at a single high dose; thus, this study examined the analgesic efficacy of a combination of fentanyl and Yokukansan (YKS). Methods: Rats were divided into control, formalin-injected (FOR), YKS-treated+FOR (YKS), fentanyl-treated+FOR (FEN), and YKS+FEN+FOR (YKS+FEN) groups. Acute pain was induced via subcutaneous injection of formalin into the paw. The time engaged in pain-related behavior was measured. Results: In the early (0–10 min) and intermediate (10–20 min) phases, pain-related behavior in the YKS+FEN group was significantly inhibited compared with the FOR group. In the late phase (20–60 min), pain-related behavior in the FEN group was the longest and significantly increased compared with the YKS group. We explored the influence on the extracellular signal-regulated kinase (ERK) pathway in the spinal cord, and YKS suppressed the phosphorylated ERK expression, which may be related to the analgesic effect of YKS in the late phase. Conclusions: These findings suggest that YKS could reduce the use of fentanyl and combined use of YKS and fentanyl is considered clinically useful. Full article

Background: Considering the anti-inflammatory properties of the Japanese traditional Kampo medicine Boiogito (BO), we aimed to investigate the therapeutic effect of BO to prevent the development of knee osteoarthritis (KOA) in rats with surgically induced KOA. Methods: Destabilization of the medial meniscus (DMM) was performed to induce osteoarthritis in the right knees of 12-week-old Wistar rats under general anesthesia. The rats were orally administered 3% BO in standard powder chow for 4 weeks after surgery (controls: n = 6; sham group: n = 6; DMM group: n = 5; DMM + BO group: n = 5). During this period, the rotarod test was performed to monitor locomotive function. After 4 weeks, histological assessment was performed on the right knee. Results: Oral administration of BO improved locomotive function in the rotarod test. Walking time on postoperative days 1, 14, or later was significantly longer in the DMM + BO group than in the DMM group. Histologically, the DMM group showed significant progression of KOA, which, in the DMM + BO group, was strongly suppressed, as assessed by the Osteoarthritis Research Society International score. Conclusions: Our results showed that oral administration of BO had a clinically preventive effect on early stage posttraumatic KOA. Full article

Background: Preoperative anxiety causes profound psychological and physiological reactions that may lead to a worse postoperative recovery, higher intensity of acute and persistent postsurgical pain and impaired quality of life in the postoperative period. Previous randomized controlled trials (RCTs) suggest that auricular acupuncture (AA) is safe and effective in the treatment of preoperative anxiety; however there is a lack of systematic evidence on this topic. Therefore, this protocol was developed following the PRISMA guidelines to adequately evaluate the existing literature regarding the value of AA for the reduction in anxiety in patients in a preoperative setting, compared to other forms of acupuncture, pharmacological, or no control interventions and measured with questionnaires regarding anxiety and fear. Methods: The following databases will be searched: MEDLINE (PubMed), EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), ISI Web of Science, and Scopus Database. RCTs will be included if an abstract is available in English. Data collection and analysis will be conducted by two reviewers independently. Quality and risk assessment of included studies will be done using the Cochrane 5.1.0 handbook criteria and meta-analysis of effectiveness and symptom scores will be conducted using the statistical software RevMan V.5.3. Conclusions: This systematic review will evaluate the efficacy and safety of AA for preoperative anxiety. Since all data used in this systematic review and meta-analysis have been published, this review does not require ethical approval. The results may be published in a peer-reviewed journal or be presented in relevant conferences. Registration number: PROSPERO ID CRD42020. Full article

Background: According to past studies, recovery and survival following severe vascular events such as acute myocardial infarction and stroke are negatively impacted by vitamin D deficiency. However, the national estimate on disability-related burden is unclear. We intend to evaluate the prevalence and outcomes of vitamin D deficiency (VDD) among patients with cardiovascular disease (CVD) and cerebrovascular disorder (CeVD). Methods: We performed a cross-sectional study on the Nationwide Inpatient Sample data (2016–2017) of adult (≥18 years) hospitalizations. We identified patients with a secondary diagnosis of VDD and a primary diagnosis of CVD and CeVD using the 9th revision of the International Classification of Diseases, clinical modification code (ICD-10-CM) codes. A univariate and mixed-effect multivariable survey logistic regression analysis was performed to evaluate the prevalence, disability, and discharge disposition of patients with CVD and CeVD in the presence of VDD. Results: Among 58,259,589 USA hospitalizations, 3.44%, 2.15%, 0.06%, 1.28%, 11.49%, 1.71%, 0.38%, 0.23%, and 0.08% had primary admission of IHD, acute MI, angina, AFib, CHF, AIS, TIA, ICeH, and SAH, respectively and 1.82% had VDD. The prevalence of hospitalizations due to CHF (14.66% vs. 11.43%), AIS (1.87% vs. 1.71%), and TIA (0.4% vs. 0.38%) was higher among VDD patients as compared with non-VDD patients (p < 0.0001). In a regression analysis, as compare with non-VDD patients, the VDD patients were associated with higher odds of discharge to non-home facilities with an admission diagnosis of CHF (aOR 1.08, 95% CI 1.07–1.09), IHD (aOR 1.24, 95% CI 1.21–1.28), acute MI (aOR 1.23, 95% CI 1.19–1.28), AFib (aOR 1.21, 95% CI 1.16–1.27), and TIA (aOR 1.19, 95% CI 1.11–1.28). VDD was associated with higher odds of severe or extreme disability among patients hospitalized with AIS (aOR 1.1, 95% CI 1.06–1.14), ICeH (aOR 1.22, 95% CI 1.08–1.38), TIA (aOR 1.36, 95% CI 1.25–1.47), IHD (aOR 1.37, 95% CI 1.33–1.41), acute MI (aOR 1.44, 95% CI 1.38–1.49), AFib (aOR 1.10, 95% CI 1.06–1.15), and CHF (aOR 1.03, 95% CI 1.02–1.05) as compared with non-VDD. Conclusions: CVD and CeVD in the presence of VDD increase the disability and discharge to non-home facilities among USA hospitalizations. Future studies should be planned to evaluate the effect of VDD replacement for improving outcomes. Full article

Background: The objective of this study was to report the incidence of in-hospital serum ionized calcium derangement and its impact on mortality. Methods: We included 12,599 non-dialytic adult patients hospitalized at a tertiary medical center from January 2009 to December 2013 with normal serum ionized calcium at admission and at least 2 in-hospital serum ionized calcium values. Using serum ionized calcium of 4.60–5.40 mg/dL as the normal reference range, in-hospital serum ionized calcium levels were categorized based on the presence of hypocalcemia and hypercalcemia in hospital. We performed logistic regression to assess the relationship of in-hospital serum ionized calcium derangement with mortality. Results: Fifty-four percent of patients developed new serum ionized calcium derangements: 42% had in-hospital hypocalcemia only, 4% had in-hospital hypercalcemia only, and 8% had both in-hospital hypocalcemia and hypercalcemia. In-hospital hypocalcemia only (OR 1.28; 95% CI 1.01–1.64), in-hospital hypercalcemia only (OR 1.64; 95% CI 1.02–2.68), and both in-hospital hypocalcemia and hypercalcemia (OR 1.73; 95% CI 1.14–2.62) were all significantly associated with increased in-hospital mortality, compared with persistently normal serum ionized calcium levels. Conclusions: In-hospital serum ionized calcium derangements affect more than half of hospitalized patients and are associated with increased in-hospital mortality. Full article

Background:Cocculus hirsutus (L.) W.Theob. (Menispermaceae) is a perennial climber distributed mostly in tropical and subtropical areas. The main aim of this article is to collect and analyze the scientific information related to traditional uses, bioactive chemical constituents and pharmacological activities. Methods: Scientific information on C. hirsutus was retrieved from the online bibliographic databases (e.g. MEDLINE/PubMed, SciFinder, Web of Science, Google Scholar and Scopus). Information regarding traditional uses was also acquired from secondary resources including books and proceedings. Results: Different plant parts of C. hirsutus were reported to be used for the treatment of fever, skin diseases, stomach disorders and urinary diseases. Alkaloids such as jasminitine, hirsutine, cohirsitine and their derivatives along with a few flavonoids, triterpene derivatives and volatile compounds were reported from whole plant or different plant parts. Extracts were evaluated for their antimicrobial, antidiabetic, immunomodulatory and hepatoprotective activities among others. Conclusion: Although widely used in traditional medicines, only a few studies have been performed related to chemical constituents. Most of the biological activity evaluations were carried out using in vitro evaluation methods and only a few studies were carried out in animal models. In the future, properly designed in vivo and clinical studies are necessary to evaluate the pharmacological activities of C. hirsutus along with bioassay-guided studies to isolate and identify the active constituents. Full article

Background: Polymyalgia Rheumatica (PMR) is one of the most frequent rheumatologic immune-related adverse effects (IRAEs) in cancer patients following therapy with immune checkpoint inhibitors (ICIs). Atypical findings in many patients often lead to diagnosing PMR-like syndromes. Materials and methods: The aim of our research was to review reported diagnoses of PMR and PMR-like syndromes following ICIs therapy, and assess whether they can be redefined as adverse drug reaction (ADR). In line with PRISMA guidelines, we carried out a systematic search on three main bibliographic databases, based on a combination of subject headings and free text. We included all studies and case-reports published after 2011 (when FDA approved the use of the first ICI) describing the association of PMR or PMR-like syndromes with all types of ICIs therapy. We excluded reviews, conference abstracts, comments, secondary articles, and non-English language studies. Results: We reviewed data from seven studies and eight case-reports, involving a total of 54 patients. Limitations included: the small size of all studies; only one retrospective study used validated criteria for PMR; most reports assessed IRAEs by clinical judgment only and did not seek validation through assessment scales. To date, it remains a conundrum whether IRAEs-PMR is identical to the idiopathic form of the disease, or whether it should be considered a subset of the disease or a new entity. Conclusions: Our review indicates that the relationship between PMR and ICIs therapy is yet to be clearly understood and defined and that future research should remedy the current limits in study design. Full article